EXP-1 is a well-characterized integral membrane protein localized to the parasitophorous vacuole [43,44]. unlikely to play a role in pathogenesis based on their annotation or localization, and proteins that behave promiscuously in the two-hybrid assay, resulting in a final dataset of 456 interactions. A cluster that implicates binding betweenP. falciparumPFE1590w/ETRAMP5, a putative parasitophorous vacuole membrane protein, and human apolipoproteins ApoA, ApoB and ApoE was selected for further analysis. Different isoforms of ApoE, which are associated with different outcomes of malaria infection, were shown to display differential interactions with PFE1590w. == Conclusion == A dataset of interactions between proteins ofP. falciparumand those of its human host was generated. The preferential interaction of theP. falciparumPFE1590w protein with the human ApoE 3 and ApoE 4 Rabbit polyclonal to AMACR isoforms, but not the ApoE 2 isoform, supports the hypothesis that ApoE genotype NVP-BSK805 dihydrochloride affects risk of malaria infection. The dataset contains other interactions of potential relevance to disease that may identify possible vaccine candidates and drug targets. == Background == Malaria is a devastating global disease, responsible for approximately 500 million clinical cases and more than a million deaths per year [1]. The most deadly form is caused byPlasmodium falciparum, which has a complex life cycle. The parasite is delivered to the human NVP-BSK805 dihydrochloride bloodstream as sporozoites that develop in the salivary gland of infected mosquitoes. These motile forms enter NVP-BSK805 dihydrochloride the liver, transversing through NVP-BSK805 dihydrochloride several cells before establishing themselves in a hepatocyte. Within the hepatocyte, the parasite undergoes a large number of asexual divisions, eventually releasing tens of thousands of merozoites that are capable of attaching to and invading erythrocytes. Within the erythrocyte, the parasite again divides several times in a 48-hour timeframe, releasing 16 or more merozoites that invade new erythrocytes. This intraerythrocytic stage is responsible for the cyclic symptoms of human disease (reviewed in [2]). As a consequence of its life cycle,P. falciparummust be able to recognize, bind to and invade at least the two human cell types of hepatocytes and erythrocytes. These events are defined by particular molecular interactions. For example, hepatocyte invasion requires binding of the parasite’s circumsporozoite surface protein to heparan sulfate proteoglycan surface receptors [3], although otherP. falciparumproteins have been implicated in this process [4]. ManyP. falciparumproteins have been proposed to be involved in erythrocyte invasion, and the human receptors for a few of them have been characterized (for example, EBA-175/glycophorin A and EBA-140/glycophorin C, MSP1/band3); however, the receptors for most of the parasite proteins implicated in erythrocyte invasion remain to be identified (reviewed in [5,6]). In both hepatocytes and erythrocytes, the parasite is contained in a membranous structure known as the parasitophorous vacuole. Within this structure, however, the parasite is not isolated from the host cell, and must import nutrients from the plasma and the host cell cytoplasm to survive [7]. Particularly in the NVP-BSK805 dihydrochloride case of erythrocyte invasion,P. falciparumalso establishes an active export of its proteins to the cytoplasm and surface of the host cell, where they modify the surface’s structural and adhesive properties (reviewed in [8]). The presence of parasite proteins, such as PfEMP1 and other adhesins on the surface of erythrocytes, causes these infected cells to sequester to endothelia and placenta via interactions with surface receptor molecules such as CD36, chondroitin sulfate A, ICAM-1 and selectins, resulting in the evasion of these cells from the host immune system. In addition, several parasite proteins interact with human cytoskeletal proteins; for example, PfEMP3 interacts with spectrin and actin [9], and both RESA and KAHRP interact with spectrin [10,11]. Previously, a large network of interactions among the proteins ofP. falciparumwas generated [12]. The results of a similar high-throughput yeast two-hybrid analysis aimed at detecting interactions between proteins ofP. falciparumand those of its human host are presented here. An initial dataset of over 2,200 putative interactions was curated to exclude interactions that are not likely.